In the early 1980s, HIV infection emerged as a rapidly progressive, terminal illness for which treatment was limited to the alleviation of pain and other symptoms at the end of life.(1) The development of effective combination antiretroviral therapy (ART) in the mid-1990s transformed HIV, at least in resource-rich settings, from a terminal to a chronic condition. Advances in treatment have dramatically changed the lives of many patients, their loved ones, and their caregivers by restoring patients to health and delaying death, even restoring to some the expectation of having an average lifespan. However, as patients are living longer, new challenges have emerged, including treatment toxicities and drug resistance; increased rates of comorbid diseases such as chronic liver and kidney disease, atherosclerosis, cancers, depression, and dementia; and issues of adherence to complex treatment regimens. In addition, HIV infection continues to be a highly prevalent and rapid killer in low- and middle-income countries, where ART is unavailable to 70-80% of patients for whom it might be beneficial.(2)
Regardless of the degree of resource availability within a given setting, the roles of pain and symptom management, psychosocial and spiritual support for patient and loved ones, and retention of hope for a peaceful and dignified death remain as vital as they were in the early days of the epidemic. The range of disease experiences, from the time of diagnosis until end-stage disease, creates many opportunities for palliation throughout the course of illness.(1) This chapter will explore the many roles of palliation and palliative care in the ART era.
| Pain Management|
HIV disease and its treatment are associated with significant pain syndromes causing morbidity, decline in function, and decreased quality of life.(5) Pain in HIV infection has multiple etiologies, including the infection itself, opportunistic infections, AIDS-related malignancies, and medication toxicities. Estimates of the prevalence of pain among HIV patients range from 40% to 60%.(6,7,8) There are limited data on the prevalence of pain in the developing world, but judging from the extent of disease, the use of older, more toxic first-line ART regimens, and limitations on access to opiates, uncontrolled pain is most likely a reality for many patients.(9,10) Strikingly, the 26 most developed nations use 90% of the world's morphine supply; the remaining 10% is distributed among developing nations bearing the brunt of HIV infection.(11)
Pain is underrecognized and undertreated in as many as 60-85% of HIV patients in the developed world.(7) Clinician barriers include inadequate knowledge of pain management, concerns regarding use of opioids, and lack of access to pain management specialists.(12) Clinicians understandably worry about addiction in their patients with substance abuse histories. Despite these concerns, physicians and nurses have an ethical obligation to treat pain and should possess knowledge and skills in basic pain management. For example, patients with histories of injection drug use often need higher dosages of opioids than others as a result of their increased tolerance to these medications. For patients on maintenance methadone, the single daily dose of medication does not treat pain.(13,14) Providers and patients should understand that the goal of pain management is to maintain function and to control pain, and that complete resolution of pain may not be possible.(15) Setting goals and writing pain contracts with patients at high risk of abuse can be useful techniques.
It is important to look for and treat the underlying etiology of pain. For example, HIV infection itself is associated with significant neurotoxicity related to viral load levels.(16) The best treatment for this kind of pain is ART, in this situation both a palliative and disease-modifying treatment. In addition, ART-associated neuropathic pain syndromes, particularly associated with certain nucleoside reverse transcriptase inhibitors such as didanosine, stavudine, and to a lesser extent, zidovudine, are regularly encountered. Changing medications, or in the case of stavudine, reducing the dosage from 40 mg twice daily to 30 mg or 20 mg twice daily, may decrease pain.(16) At the same time, if disease-specific interventions do not work, it is important to address the pain directly.(16) Figure
1 shows a "pain ladder" model developed by the World Health Organization (WHO) for progressive treatment of pain.(17) The basis of the ladder is the 3-step approach, starting with nonopioids for mild pain, escalating to mild opioids for moderate pain, and moving to stronger opioids for severe pain until the pain is controlled. For anything but mild pain, medications should be given around the clock rather than on demand. Adjuvants, such as certain antidepressants, anticonvulsants, nonsteroidal antiinflammatory drugs (NSAIDs), and muscle relaxants, should be used as appropriate, depending on the type of pain (see Table
| Symptom Management|
HIV infection is associated with a wide spectrum of symptoms related to the infection itself, opportunistic infections, and treatment side effects. Addressing these symptoms improves quality of life and may improve treatment adherence. (See the HIV InSite Knowledge Base chapter Symptom Management Guidelines.) The most prevalent and distressing symptoms are weight loss, anorexia, fatigue, nausea, vomiting, anxiety, depression, cough, fever, and dyspnea.(6) As with pain, treatment of the underlying cause of the symptom may relieve the discomfort. On the other hand, when disease-specific treatments are inadequate, symptom-specific approaches are indicated. Table
2 outlines treatments for common symptoms.
| Communication and Difficult Conversations|
Communication is an essential part of the provider-patient relationship. There are many difficult discussions that HIV providers must initiate, including the delivery of bad news, clarifying treatment options, exploring values and goals of care, and discussing prognosis and advance care planning. For patients and their loved ones, these conversations often occur at times of crisis or provoke a state of crisis; emotions can be raw. Providers need to use good communication techniques, including asking open-ended questions, listening carefully, and gauging patients' understanding of the issues at hand. In all these conversations, patients should do the majority of the talking. Providers should acknowledge emotions and use empathic statements. Discussion of advance directives and establishment of the patient's choice of a surrogate decision maker ideally should happen early in the course of disease progression. Clinicians can encourage the patient to fill out the appropriate paperwork to formally assign a durable power of attorney for health care. Although patients' decisions can change during the course of illness, it is helpful to begin these discussions to establish a baseline sense of the patient's beliefs and values. Table
3 gives examples of useful questions and phrases for initiating and deepening these discussions.
HIV patients, as with other patients, may resist talking about end-of-life issues. There is evidence that this hesitance is particularly prominent among patients from minority groups and those who use drugs.(18,19) Patients may be reluctant to face their mortality and may distrust providers who bring up end-of-life issues, fearing discrimination and early, inappropriate withdrawal of life-sustaining measures.(18,19,20)
| Prognostication and Discussions of Prognosis|
There are many important reasons to discuss prognosis. Many patients want to know their prognosis and expect the physician to bring up the subject. Understanding prognosis changes patients' decisions about treatments and gives them time to address issues of life closure, such as saying good-bye to loved ones, thinking about legacy and spirituality, and settling financial affairs. Failure to address prognosis can engender "false hope" and result in patients spending their last days in a hospital in pain, receiving more aggressive treatments than they might have wanted if they understood they were dying.(21)
Discussing prognosis with patients can present difficulties stemming from providers' personal feelings and anxieties about death, fears of taking away hope, and lack of training and time. In addition, clinicians worry that their predictions will be incorrect. In the most comprehensive study to date of prognostication, physicians overestimated patient survival by a factor of 5 on average.(22) Nonetheless, providers can still discuss prognosis in a way that is truthful, if they acknowledge uncertainty. They can couch prognosis in terms of ranges (eg, "months to a year," "weeks to months," "days to weeks") and explain that some people outlive and some "under-live" their prognosis.
Estimates of survival for HIV patients in the United States with access to current treatment regimens are 24 additional years.(23) Some research has shown that traditional markers for disease progression such as CD4 count and viral load may not correlate clearly with prognosis in patients with advanced HIV infection, further complicating end-of-life discussions and decision making.(24) Measures of functional status, such as the Karnofsky score (25) and the Palliative Performance Scale,(26) may better predict mortality. And, in contrast to the more predictable, consistently worsening disease trajectories seen with a terminal cancer, HIV illness can be punctuated by episodes of worsening function (resulting from infection, toxicity, or increased symptoms) followed by periods of improvement or symptom-free living that do not necessarily signal a progression of illness.(27) Perhaps the most important change in the ability to predict an HIV-infected patient's prognosis has been the observation that the initiation of effective combination ART can restore health to many patients who have conditions such as wasting, chronic diarrhea, or intractable opportunistic infections that would have predicted death in the pre-ART era. This uncertain disease trajectory underscores the importance of pain, symptom management, good communication, clarification of patients' goals, and advance care planning throughout the course of illness. Despite the uncertainty around prognosis, there are guidelines for prognostication and for hospice eligibility. (See End-of-Life Care and Hospice, below, and Table
| Psychosocial and Spiritual Support|
Clinicians worry that acknowledging the inevitability of death will cause patients to lose hope. Most patients, however, understand that they are getting sicker, and they expect clinicians to initiate discussions about death and dying.(1,28,29) It is important to recognize that patients can hope for many things other than the cure of their illness. For example, they can hope for good control of their symptoms so they can spend meaningful time with family and friends, heal troubled relationships, create a legacy, and say good-bye. As in other developmental stages throughout life, the process of dying can be a time of emotional and spiritual growth and provide an opportunity to deepen relationships and find greater meaning.(30) Despite their fears, physicians are much less likely than they think to take away hope. In fact, doctors can help patients to refocus on more attainable goals, thereby reinstating hope into what may be perceived as a hopeless situation.(31,32)
An interdisciplinary palliative care team can work together to address the wide variety of patient concerns though the course of illness. Addressing emotional, social, and existential concerns is impossible for a single provider; rather, it takes a team of clinicians with different but complementary backgrounds. Social workers, chaplains, and psychologists can enormously enhance the support provided by physicians, nurses, and nurse practitioners. Further, members of the team can support one another in their own emotional reactions to caring for patients with serious illness. They can help themselves and members of the primary team to grieve the death or worsening of patients for whom they care deeply.(30)
The role of the interdisciplinary team is particularly important when patients are making a transition from life-prolonging medical intervention to comfort measures. At this vulnerable time, patients and loved ones may worry about a loss of support from their medical team, especially if clinic visits become less frequent or stop altogether. It is important to reassure patients that choosing comfort care or hospice does not signify a "loss of care" or abandonment by the care team. If a patient becomes too sick to attend clinic, it is paramount to offer assurances that the patient will continue to be well-cared for and to ensure continuity with the new providers.
Psychosocial support does not end with the death of the patient. The palliative care team can reach out to survivors and provide bereavement support or referrals for bereavement counseling. Writing letters or making phone calls to loved ones after a death can be incredibly meaningful and can help soften some of the pain. In addition, family members or friends may have outstanding and important questions that providers can address in these phone calls.
| End-of-Life Care and Hospice|
Hospice is comprehensive care at the end of life for patients who want to focus their care on comfort and quality of life. It can occur in the patient's home, a residential facility, or a nursing home. It is also an insurance benefit; to qualify in the United States, patients must have a prognosis of 6 months or less and must decline treatments whose main goals are to lengthen life. Such treatments include surgeries, chemotherapy, or radiation procedures that are not clearly palliative, and inpatient treatments such as intravenous antibiotics and anticoagulants. The majority of hospice care in the United States occurs in the home, where family members or paid attendants perform the majority of routine care. The hospice team, led by a nurse, comes to the home as needed, often biweekly or more frequently, depending on patient and family needs. Deciding whether to continue ART as a palliative measure is often difficult. Weighing the burden-to-benefit ratio over time, although complicated, often leads patients, as they get sicker, to stop treatments such as ART because of side effects or the burden of taking pills.(33) ART is expensive and some hospices need to look for creative ways to pay for it.(34) Providing excellent end-of-life care is particularly challenging when patients have limited or no income, family support, or housing. Table
4 summarizes the National Hospice Organization's guidelines for hospice eligibility, as modified by Peter Selwyn for the era of effective ART.
As with ART and other treatments, the issue of access remains a serious issue for palliative care in resource-limited settings.(36,37,38,39) International health organizations including the WHO recognize the importance of adequate pain control, symptom management, and psychosocial support as part of the equitable distribution of health resources.(40) Resource-poor communities face a multitude of barriers including overwhelming numbers of patients, underdeveloped health care systems, racial and ethnic disparities in access to health care, and limited access to opioids.(41) As mentioned, various models and programs are being adapted to developing countries. Most notable are those designed on the "integrated community-based home care" (42,43) model, utilizing community caregivers in home settings. More training, funding, and support are needed to strengthen these programs and extend their reach. Lastly, there are unique psychosocial challenges to end-of-life care in much of the developing world. Huge numbers of orphaned children stress the support systems in place, women in general carry a greater economic burden and also bear most of the responsibility for care giving, and stigma against HIV-infected patients is rampant.(37)